The purpose of the proposed study is to investigate the effects of a regular, moderate exercise program on the immune response to influenza immunization in older adults; and to determine whether the mechanisms of the exercise-induced immunomodulation involve psychosocial and/or neuroendocrine adaptations. Older adults experience a greater incidence and severity of influenza infection, as well as reduced vaccine efficacy. We hypothesize that exercise will enhance immune response to the vaccine and improve psychosocial state. A total of 72 men and women > age 65 will be assigned to an exercise (EX), n=36, or control (CON) group, n=36. An additional 32 subjects (n= 16 EX, n=16 CON) currently treated with non-selective beta-adrenergic receptor antagonists will be recruited to test the hypothesis that the immunomodulatory effects of exercise are mediated via catecholamine activation of beta-adrenergic receptors. Subjects will be immunized with influenza vaccine and will be randomly assigned to participate in either a regular vigorous aerobic exercise program (EX) or a flexibility program (CON) for one year. Blood samples will be taken pre and post-immunization. At the end of one year, subjects will be immunized again and blood samples will be taken pre-immunization and up to 6 months post-immunization. Psychosocial measures of depression, perceived stress, social support, positive/negative affect, and daily hassles/uplifts will be assessed numerous times throughout the study. The primary immune outcome measures are: anti-influenza IgG and IgG1, influenza specific peripheral blood mononuclear cell proliferation and cytokine (interleukin (lL)-2, IL-10, interferon (IFN)-gamma) production, cytotoxic T lymphocyte (CTL) function, and intracellular influenza-specific IL-2, IL-b 0, IFN-gamma, in CD4+, CD8+, CD45RA+ and CD45RO+ cells. Growth curve modeling will be used to analyze the relationship between treatment condition and changes in the measures of immunocompetence over time. The findings from this study may have relevance from both a clinical and basic research perspective, if moderate exercise is associated with enhanced anti-influenza immunity and improved protection from infection.